Pharmaceutical composition made from hydrophobic phytochemicals dispersed in sesame oil to enhance bioactivity

ABSTRACT

Pharmaceutical formulations and methods to increase the bioactivity and bioavailability of plant compound having hydrophobic phytochemicals which have poor bioavailability due to poor water solubility. Dispersions of extracts of  Boswellia  and/or  Curcuma longa  in sesame seed oil. Analgesic and anti-inflammatory composition having a) an extract of  Boswellia , b) one or more of an extract of  Curcuma longa , a curcuminoid composition and combinations thereof, and, c) a sesame seed oil. The analgesic and anti-inflammatory composition has particles having a particle size ranging from less than about 20 micrometers to about 1 micrometer. The analgesic and anti-inflammatory composition provides a total combined specific surface area provided by particles in the composition ranging from about 900 meter 2  per kilogram to about 3000 meter 2  per kilogram of the composition. Methods of preparing the compositions and methods of treating inflammation and musculoskeletal disorders are provided.

FIELD

The disclosure relates to nano-particle dispersion in oil, such asformulation made from hydrophobic phytochemicals dispersed in sesame oilto enhance bioactivity. The formulation is standardized into a specificformulation, product and dosage. The formulation can be used in naturaldietary and health supplementation. The disclosure also relates to amethod to increase bioavailability of water-insoluble plant compounds.The disclosure also relates to a method of manufacturing the formulationand use of the product in the treatment of chronic inflammation,arthritis, crohn's disease, asthma, osteoarthritis, lupus, rheumatoidarthritis, and inflammatory bowel disease.

BACKGROUND

Herbal products are more often linked to health and recommended ashealth supplements. These herbal products more often derive their rootfrom traditional medicines, but unlike traditional medicines modernherbal products are tested against modern medicines. Activephytochemicals are being identified, standardized and new products arebeing developed. Phytochemicals are gaining popularity because of havingfewer side effects. But unlike synthetic drugs, herbal products havepoor bioavailability and, therefore, the dosage required for medicinalformulation is much higher.

When drugs are administered orally, it passes through multiple barriersbefore it can reach the bloodstream and this lead to drug wastage. Theproportions of drug that make it to the bloodstream on oraladministration determine the bioavailability of drugs. Bioavailabilityof drugs determines its dosage and applicability.

Among the phytochemicals, some are lipid soluble and some water-soluble,and the latter has a greater likelihood of making it to the systemiccirculation. Sometimes the lipid soluble or hydrophobic phytochemicalshave advanced potency but because of poor bioavailability fails todeliver. Higher dosage is required in case of phytochemicals with poorbioavailability because of drug wastage.

There are many ways to increase the bioavailability of phytochemicals.According to U.S. Pat. No. 7,883,728B2, bioavailability of curcumin isenhanced by linking the curcuminoids with Ar-turmerone, and theformulation produced a synergetic effect.

In US 2013/0084348A1 the non-polar boswellia extract is used asbio-enhancing agents for biological agents such as amino acid,nutrients, vitamins. Boswellia extract has its own activity, Boswelliaacid derived from boswellia has anti-inflammatory activity. Boswellicacids seem to be specific inhibitor of 5-LO, which is one of the enzymethat is responsible for inflammation.

In WO2017068600 A1 the bioavailability of withanolide glycosides andsaponins derived from Withania somnifera is enhanced by delivering themdirectly in intestine and avoiding release in stomach altogether.Providing enteric coating or sustained release is one of the methods toincrease the bioavailability and bioactivity of a drug, or compoundsderived from plant.

One method of improving bioavailability of drugs is by reducing theparticle size of the plant derivatives. As the partial size reducesthere are significant changes in the property is observed. A particle atnano-scale is made up of fewer molecules which results in high energygap, which can be a reason for improvement in the bioavailability.

One method of improving bioavailability of drugs is by reducing theparticle size of the plant derivatives. As the particle size reducesthere are significant changes in the property is observed. A particle atnano-scale is made up of fewer molecules which results in high energygap, which can be a reason for improvement in the bioavailability.Another reason is the increased surface are that increases the reactionarea enabling it to be absorbed in to blood.

Sesame oil, boswellia extract and cucuminoids all have some level ofanalgesic or anti-inflammatory property, but not particularly uses thesame mechanism to inhibit pain and inflammation. A combination of thethree can provide a comprehensive action against pain and inflammationespecially in inhibiting lipoxygenase, cyclooxygenase or NF-kB. Sesameoil being a lipid can be used as a carrier medium but only 2% ofboswellia extract and curcuminoid mixture can be loaded in to sesameoil. A method is required to load more boswellia extract or curcuminoidsin to sesame oil and obtain a stable product where the loaded extractsdo not precipitates or settle down.

OBJECTIVES

The primary objective is to enhance bioavailability of phytochemicalswith poor bioavailability and is poorly water-soluble or hydrophobic innature.

Another objective is to have a formulation with nano-scale ormicro-scale plant particles stabilised by dispersing uniformly in an oilto improve bioactivity and bioavailability.

One more objective is to develop a method to make dispersion with microto nano-particle size active ingredients dispersed in it. Yet anotherobjective is to develop a method to manufacture a bioactive formulationand composition.

SUMMARY

Analgesic and anti-inflammatory composition having a) an extract ofBoswellia, b) one or more of an extract of Curcuma longa, a curcuminoidcomposition and combinations thereof, and, c) a sesame seed oil isdisclosed. The particles of extract of Boswellia and extract of Curcumalonga or a curcuminoid composition are dispersed in sesame oil. Theparticle size ranges from less than about 20 micrometre to about 1micrometre. The analgesic and anti-inflammatory composition provides atotal combined specific surface area provided by particles in thecomposition. The total combined surface area of the particles in thecomposition ranges from about 900 meter² per kilogram to about 3000meter² per kilogram of the composition. The particle can have componentsa), b), a combination of a) and b), or combinations thereof.

An anti-inflammatory and anti-analgesic composition of a) an extract ofBoswellia, b) one or more of an extract of Curcuma longa, a curcuminoidcomposition and combinations thereof, and, c) a sesame seed oil, wherethe composition is in the form of a dispersion is provided. Thedispersion has particles. The particles can have components a), b), acombination of a) and b), or combinations thereof.

In some embodiments of the analgesic and anti-inflammatory composition,the particle size of the particle ranges from less than about 20micrometers to about 1 micrometer.

In some embodiments a dosage form of the analgesic and anti-inflammatorycomposition is provided. The composition in the dosage form is in theform of a dispersion having particles. About 50% of the particles in thedosage form of the composition have a particle size of less than about 5micrometer.

In some embodiments, a weight ratio of components a):b):c) ranges fromabout 1:1:1 to about 5:1:99. In some embodiments, a weight ratio ofcomponents a):b):c) is about 3:1:6.

In some embodiments, the sesame seed oil includes about 30% to about 70%sesame lignans. In some embodiments, the sesame lignans are in a weightratio of sesamin:sesamolin of about 1:1.

The extract of Boswellia in the anti-inflammatory and anti-analgesiccomposition includes about 1% to about 30% acetyl-11-keto-beta-boswellicacid. In some embodiments, the extract of Boswellia includes about 10%acetyl-11-keto-beta-boswellic acid.

The curcuminoid composition in the anti-inflammatory and anti-analgesiccomposition includes a curcuminoid mixture and an essential oil ofturmeric. The curcuminoid composition includes curcumin,demethoxycurcumin and bisdemethoxycurcumin. In some embodiments, theessential oil of turmeric includes at least about 15% ar-turmerone. Insome embodiments, the essential oil of turmeric includes about 40 toabout 50% ar-turmerone. In some embodiments, the essential oil ofturmeric includes at least about 15% alpha turmerone.

A dosage form of the anti-inflammatory and anti-analgesic composition isprovided. The dosage form can be hard gel capsule, soft gel capsule,paste, ointment, infusion, injection, ampoule, solution, suspension,emulsion, oil or cream.

A method of treating inflammation in a subject in need thereof isprovided. The method includes administering an effective amount of theanalgesic and anti-inflammatory composition.

The method includes administering an effective amount of the analgesicand anti-inflammatory composition. The subject is treated for conditionssuch as low back pain, general whole body pain, myalgia, headache, neckpain, limb pain, grade one sprain, joint pain, acute soft tissue injury,acute injuries of ligaments and acute injuries of tendons. The method oftreatment includes inhibiting one or more of lipoxygenase,cyclooxygenase and NF-kB. Methods of treatment include administering theanalgesic and anti-inflammatory composition whereby a Numerical RatingScale shows an improvement of about 70% in about 6 hours afteradministering the composition. In some embodiments, the Numerical RatingScale shows an improvement of about over 80% after administering thecomposition every day for 7 days. In some embodiments of the method oftreatment, a Pain Relief Scale (PRS) improves about 75% in about 6 hoursafter administration the composition. In some embodiments of the methodof treatment, a Pain Relief Scale improves about 75% after administeringthe composition for 7 days. In some embodiments of the method oftreatment, Meaningful Pain Relief is observed within 5 min afteradministering the composition.

Methods of preparing an analgesic and anti-inflammatory composition areprovided. The composition includes a) an extract of Boswellia, b) one ormore of an extract of Curcuma longa, a curcuminoid composition andcombinations thereof, and, c) a sesame oil. The method or preparationincludes mixing a), b) and c) to obtain a mixture. The composition issubjected to milling, and repeating the milling of the compositionseveral times till the particle size is as required. The particles havea particle size ranging from less than about 20 micrometre to about 1micrometre. The total combined surface area provided of particles in thecomposition ranges from about 900 meter² per kilogram to about 3000meter² per kilogram of the composition. The particle can have componentsa), b), a combination of a) and b), or combinations thereof.

An analgesic and anti-inflammatory composition having an extract ofBoswellia, and, a sesame oil is provided. The particles of extract ofBoswellia are dispersed in sesame oil The particles having a particlesize ranging from less than about 20 micrometre to about 1 micrometre.The analgesic and anti-inflammatory composition provides a totalcombined specific surface area provided by particles in the composition.The total combined surface area of the particles in the compositionranges from about 900 meter² per kilogram to about 3000 meter² perkilogram of the composition.

Disclosure provides an extract of Boswellia and methods of preparing thesame. The extract of Boswellia includes about 10%acetyl-11-keto-beta-boswellic acid and less than about 0.1%11-keto-beta-boswellic acid. The method includes steam distilling gumresin pellets of Boswellia mixed with water. Then essential oil from thesteam distillation is collected. The water from the steam distillationis drained to obtain a first gummy residue. The first gummy residue isextracted with ethyl acetate at about 70° C. to obtain a second residueand a first supernatant. A liquid-liquid extraction of the firstsupernatant is performed by adding sodium hydroxide dissolved in firstsupernatant, water soluble part get extracted from first supernatant towater. Hydrochloric acid is added to the water soluble phase to obtain aprecipitate and a second supernatant. The precipitate is dried andpulverized to obtain a powder. The powder is the extract of Boswelliahaving about 10% acetyl-11-keto-beta-boswellic acid and about 0.1% toabout 0.3% 11-keto-beta-boswellic acid.

Methods for further enriching the 10% acetyl-11-keto-beta-boswellic acidto about 70%, the method are provided. The method includes a) dissolvingthe extract of Boswellia having about 10% acetyl-11-keto-beta-boswellicacid and about 0.1% to about 0.3% 11-keto-beta-boswellic acid in ethylacetate to obtain a solution. The solution is loaded onto a silicacolumn. The silica column is extracted with hexane to obtain a firstelute and a first eluted column. The first eluted column is extractedwith a solvent having hexane and ethyl acetate in a ratio of about 95:5to obtain a second elute and a second eluted column. The second eluteincludes about 80% beta boswellic acid and about 20% alpha boswellicacid. The second eluted column is eluted with a solvent having hexaneand ethyl acetate in a ratio of about 90:10 to obtain a third elute anda third eluted column. The third elute includes beta-boswellic acid,alpha boswellic acid and 3-O-acetyl boswellic acid. The third elutedcolumn is extracted with a solvent having hexane and ethyl acetate in aratio of about 80:20 to obtain a fourth elute and a fourth elutedcolumn. The fourth elute includes alpha boswellic acid, 3-O-acetylboswellic acid and acetyl-11-keto-beta-boswellic acid. The fourth elutedcolumn is eluded with a solvent having hexane and ethyl acetate in aratio of about 70:30 to obtain a fifth elute and a fifth eluted column.The fifth elute includes about 70% acetyl-11-keto-beta-boswellic acidand about 30% 11-keto-beta-boswellic acid. The fifth eluted column isextracted with a solvent having hexane and ethyl acetate in a ratio ofabout 60:40 to obtain a sixth elute and a sixth eluted column. The sixthelute includes about 10% acetyl-11-keto-beta-boswellic acid and11-keto-beta-boswellic acid. The sixth eluted column is extracted with asolvent having hexane and ethyl acetate in a ratio of about 20:80 toobtain a seventh elute a seventh eluted column. The seventh elutedcolumn is eluted with ethyl acetate to obtain an eighth elute. Theextract of Boswellia is any one of the first elute, the second elute,the third elute, the fourth elute, the fifth elute, the sixth elute, theseventh elute, the eighth elute, or combinations thereof.

Disclosure provides a uniform blend composition having an extract ofBoswellia and sesame oil and methods of preparing the same. The methodincludes mixing sesame oil and the extract of Boswellia to obtain amixture. Subjecting the mixture to milling repeatedly to obtain auniform blend composition whereby the uniform blend composition has aparticle having a surface area ranging from about 900 to about 3000meter² per kilogram.

An anti-inflammatory composition having an extract of Curcuma longa, acurcuminoid composition and combinations thereof, and sesame oil isdisclosed. The anti-inflammatory composition has particles having aparticle size ranging from less than about 20 micrometre to about 1micrometre. The total combined surface area of particles in thecomposition ranges from about 900 meter² per kilogram to about 3000meter² per kilogram of the composition. Methods of preparing thecomposition include mixing a) and b) to obtain a mixture, subjecting themixture to milling to obtain a homogenised blend of the composition.

BRIEF DESCRIPTION OF THE DRAWINGS

The above objectives and advantages of the disclosed teachings willbecome more apparent by describing in detail embodiments thereof withreference to the attached drawings in which:

FIG. 1: Method of obtaining boswellia extract using methanol.

FIG. 2: Method of removing boswellia oil from resin using steamdistillation.

FIG. 3: Method of enriching AKBA in steam distilled boswellia extract.

FIG. 4: Method to separate out AKBA from boswellia extracts using Columnchromatography.

FIG. 5: Method to make Boswellia extract dispersion in sesame oil usingbead mill.

FIG. 6: Method to make boswellia and curcuminoids extract dispersion insesame oil using bead mill.

FIG. 7: Graph of Numerical ratting Scale (a) from baseline to six hoursand (b) from baseline to 7 days.

FIG. 8: Graph of Pain relief scale (a) baseline to 6 hours and (b)baseline to 7 days.

FIG. 9: Graph of Perceptible pain relief and meaning full pain relief.

FIG. 10: Graph of Patients Global Impression of Change (PGIC) for sevendays.

DETAILED DESCRIPTION

Medicinal compositions are disclosed. Also disclosed are methods toenhance bioactivity of hydrophobic phytochemicals and the process tomake them. The formulation and its features are disclosed hereon throughvarious embodiments. Each embodiment describes a novel feature. Someembodiments have multiple aspects and such aspects provide the scope ofthe embodiments. Through the following embodiments, a formulation andproduct along with a process of manufacturing and method of use isdisclosed. The embodiments have to be understood in its broadest sense.

The source of plant compounds disclosed throughout the specification canbe any one or a combination of an extract, juice, lyophilized juicepowder, dried plant part power, pulp, flakes and raw plant parts.

All the ratios and proportions of blends, mixtures and combinations arein weight bases and are to be taken in weight bases if not specifiedotherwise.

Boswellic acid or boswellia acid may be used interchangeably throughoutthe specification. The Boswellic acid primarily hasAcetyl-11-keto-beta-boswellic acid (AKBA), 11-keto-β-boswellic acid(KBA), β-boswellic acid (β-BA), α-boswellic acid (α-BA), andacetyl-α-boswellic acid (AaBA).

Standard extract of boswellia as described in the specification includessolvent extract of boswellia frankincense (resin) or just boswellia oilextracted using supercritical CO₂ extract. In such boswellia extractsthe AKBA might be or might not be standardized. AKBA is not theprevalent boswellic acid in boswellia frankincense, without any specialenrichment the AKBA content in boswellia extract may stay below 5%.

The minimum particle size of powdered plant extracts goes close to 100μm and an average particle size of roughly 400 μm and more. The specificsurface area (SSA) of such extract is below 200 m²/Kg.

The specific surface area (SSA) is total surface area of a material perunit of mass, powdered and granules have high surface area compared to asolid block or a chunk of the same weight. Increased surface area meansincreased reaction area, making a drug more active than normal. At thesame time increased surface area also means the risk of agglomeration ofparticles. Increasing SSA enhances the bioavailability of the activecomponents. By loading high concentration of the plant extract into oilssuch as sesame seed oil agglomeration can be avoided. In the presentapplication the active components are the plant extract or extractcomposition. Plant extracts particle in micro or nano scale cannot beadministered directly, it needs a carrier or it will result inagglomeration. Sesame oil keeps the high energy micro or nano-particlesstable and it also acts as a carrier. The compounds with SSA of 3000m²/Kg the partial size of such compounds can go down to nano scale.

Hydrophobic plant compounds have poor bioavailability because of theirpoor dissolution rate. Enhancing the bioavailability will reduce drugwastage and improve the activity of compounds derived from plants. Itwas observed that a uniformly dispersed plant compound in sesame oil ismore active than using plant compound as such. The plant compounds weredispersed in other desolation mediums also such as coconut oil, oliveoil and rice bran oil but the best results were obtained with sesameseed oil.

Studies conducted by the inventor revealed that reduced size enabledhigher concentration of plant extracts to be dispersed or loaded in tooil. The inventor also found that such formulation made with boswelliaextract loaded in sesame oil has a greater bioavailability and fasteractivity compared to boswellia extract per se. A notable improvement wasseen in a formulation made of curcuminoid compound, water insolubleboswellia extract and sesame lignans dispersed uniformly in a lipidsolvent. The average SSA for the formulation was about 3000 m²/Kg. Plantextracts which generally form a colloidal with sesame oil are uniformlydispersed when particle size is reduced. The formulation was tested foractivity alongside a mixture of curcuminoid compound, water insolubleboswellia extract and sesame lignans dissolved in a lipid solvent with aSSA of less than 200 m²/Kg.

Sesame seed oil is bioactive oil and has multiple therapeutic benefits,but in the disclosed embodiments, sesame oil is used as a carrier toenhance the bioavailability of plant extracts with poor watersolubility. It was observed that plant extract dispersed in sesame oilhas a higher bioactivity and bioavailability compared to theircounterpart. A dispersion of plant extract in sesame oil had an efficacygreater than theoretically expected values, which signifies a synergy.

Activity of boswellia, more specifically activity of boswellic acid suchas AKBA is improved by dispersing boswellia extract in oil, specificallyin sesame oil. Blending with sesamin oil avoids the fast metabolicreduction of AKBA but simple addition boswellia into oil such as sesaminoil do not make a perfect homogenized solution, it rather become a thickcolloidal. Blending should be done in or below micron scale to getdesired results. The desired result is a uniformly suspended boswelliaacid in sesame oil.

Some embodiments also enriched AKBA in boswellia extract. Boswelliaextract is obtained from boswellia gum resin through solvent extraction.The oil part of the resin can be removed by hexane washing or bydistillation. There are many ways of making an AKBA rich boswelliaextract, such as introducing an acetyl group into boswellia extract isone of the most common methods of producing AKBA from boswellic acid.AKBA can be enriched without alkylation using silica gel columnchromatography.

An analgesic and anti-inflammatory composition is provided. Thecomposition includes a) an extract of Boswellia, b) one or more of anextract of Curcuma longa, a curcuminoid composition and combinationsthereof, and, c) a sesame seed oil. The weight ratio of a):b):c) rangesfrom about 1:1:1 to about 5:1:99. The above composition is made of 30±5%boswellia extract, 10±5% extract of Curcuma longa or curcuminoidcomposition and 60±5% sesame oil by weight. The composition is ahomogenised dispersion of boswellia extract and turmeric extract insesame oil. In other words at least a 40% loading of solid boswelliaextract, turmeric extract in sesame oil.

In some embodiments, a weight ratio of a):b):c) is about 3:1:6. Theproportion of each component in the composition; boswellia extract andextract of Curcuma longa or curcuminoid composition are in 1:1 to 5:1ratio, preferably 3:1 by weight. The boswellia extract and extract ofCurcuma longa or curcuminoid composition to sesame oil are in 1:1 to1:99 ratio, more preferably 1:1 to 1:10 by weight. Some other preferredratios are 2:3, 5:7 and 11:19.

The composition is a dispersion of micro scale or nano-particles ofboswellia extract, Curcuma longa, a curcuminoid composition andcombinations in sesame oil. The plant extracts are dispersed uniformlyin the oil to make it a homogenised solution. The analgesic andanti-inflammatory composition has particles having a particle sizeranging from less than about 20 micrometers to about 1 micrometer. Theanalgesic and anti-inflammatory composition provides a total combinedspecific surface area provided by particles in the composition. Thetotal combined surface area provided by particles in the compositionranges from about 900 meter² per kilogram to about 3000 meter² perkilogram of the composition. The particle can have components a), b), acombination of a) and b), or combinations thereof.

In the analgesic and anti-inflammatory composition the boswellia extractand extract of Curcuma longa or curcuminoid composition have aspecific-surface-area (SSA) of more than 900 m²/Kg more preferably above3000 m²/Kg. The SSA of the boswellia extract and turmeric extractdispersed in lipid solution is 5 to 15 fold greater than regularboswellia extract, more precisely 9 to 12 fold. The average particlesize of dispersed boswellia extract and turmeric extract is less than 20μm-1 μm, more precisely about 50% of particles have a particle size lessthan 5 μm.

In some embodiments, the sesame seed oil includes about 30% to about 70%sesame lignans. In some embodiments, the sesame lignans are in a weightratio of sesamin to sesamolin is 1:1.

In some embodiments the boswellia extract in the composition ispreferably a water-insoluble boswellia extract made of over 30%boswellic acid, more precisely at least 10% AKBA, less than 1% KBA,5-12% α-BA and 19-28% β-BA. The curcuminoid composition is made ofcombination of curcuminoids and essential oil of turmeric. The essentialoil of turmeric comprises ar-turmerone at least 15% by weight orα-turmerone at least 15% by weight or both. The composition is ahomogenised dispersion of Water-insoluble boswellia extract andcurcuminoid composition in sesame oil.

A dosage form of the anti-inflammatory and anti-analgesic composition isprovided. The dosage form can be hard gel capsule, soft gel capsule,paste, ointment, infusion, injection, ampoule, solution, suspension,emulsion, oil or cream. The composition could be administered to humanbeings at a dose of 50 mg to about 2000 mg. About 50% of the particlesin the dosage form of the composition have a particle size of less thanabout 5 micrometre

A method of treating inflammation in a subject in need thereof isprovided. The method includes administering an effective amount of theanalgesic and anti-inflammatory composition.

A method of treating inflammation and muscular skeletal pain in asubject in need thereof is provided. The method includes administeringan effective amount of the analgesic and anti-inflammatory composition.The subject is treated for conditions such as low back pain, generalwhole body pain, myalgia, headache, neck pain, limb pain, grade onesprain, joint pain, acute soft tissue injury, acute injuries ofligaments and acute injuries of tendons.

Methods of treatment include administering the analgesic andanti-inflammatory composition whereby a Numerical Rating Scale shows animprovement of about 70% in about 6 hours after administering thecomposition.

In some embodiments, the Numerical Rating Scale shows an improvement ofabout over 80% after administering the composition every day for 7 days.In some embodiments of the method of treatment, a Pain Relief Scale(PRS) improves about 75% in about 6 hours after administration thecomposition. In some embodiments of the method of treatment, a PainRelief Scale improves about 75% after administering the composition for7 days. In some embodiments of the method of treatment, Meaningful PainRelief is observed within 5 min after administering the composition.

The method of treatment includes inhibiting one or more of lipoxygenase,cyclooxygenase and NF-kB.

In some embodiment a powdered extract of boswellia is disclosed, wherethe ratio between AKBA to KBA is manipulated and fixed at 90:1 to 1:1,the ratio between AKBA to β-BA is fixed at 90:1 to 1:1. A much morepreferred ratio of AKBA to KBA will be 50:1 to 1:1 and more preferably30:1 to 10:1 and most preferably 20:1 to 10:1. A much more preferredratio of AKBA to β-BA is 50:1 to 1:1 and more preferably 30:1 to 1:1 andmost preferably 20:1 to 3:1.

In some embodiment an analgesic and anti-inflammatory composition madeof boswellia extract and sesame oil is disclosed. The composition is ahomogenised dispersion of boswellia extract in sesame oil.

The proportion of each component in the composition; boswellia extractto sesame oil is blended in 1:1 to 1:99 ratio, more preferably 1:1 to1:10 by weight. Some other preferred ratios are 2:3, 5:7 or 11:19.

Another aspect of the embodiment, sesame lignans to boswellic acid arein a range of 3:5-1:100 ratios, more preferably 3:5-1:25, mostpreferably 2:5 ratio.

Yet another aspect of the embodiment, sesame lignans to AKBA are in arange of 1:4-1:90, more preferably 1:4 to 1:20 and most preferably 1:8ratio.

Yet another aspect of the embodiment, sesamolin to AKBA is in a range of1:10-1:90, more preferably 1:10-1:25 and most preferably 2:25 ratio.

Yet another aspect of the embodiment, sesamin to AKBA is in a range of1:10-1:90, more preferably 1:10-1:35 and most preferably 1:25 ratio.

The boswellia extract have a specific-surface-area (SSA) of more than0.9×10³ m²/Kg more preferably above 3×10³ m²/Kg. The SSA of theboswellia extract dispersed in lipid solution is 5 to 15 fold greaterthan regular boswellia extract, more precisely 9 to 12 fold. The averageparticle size of dispersed boswellia extract is less than 20μ-1μ, moreprecisely than 50% of dispersion has a particle size less than 5 μl.

Boswellia extract is made of over 30% boswellic acid, more precisely atleast 10% AKBA, less than 1% KBA, 5-12% α-BA and 19-28% β-BA. Theboswellia extract could be derived from solvent extract, supercriticalextract, dried juice powder, or dried plant part.

Another aspect of the embodiment is a 100 mg dosage form of analgesicand anti-inflammatory composition. Table 1 provides the composition of100 mg analgesic and anti-inflammatory composition.

TABLE 1 100 mg AKBA analgesic and anti-inflammatory composition Sesameoil 56 mg Sesaminol 0.39 mg Sesamin 0.16 mg Boswellia 44 mg AKBA  4.4 mgextract KBA 0.18 mg α-BA 0.45 mg B-BA 1.16 mg Total BA 14.52 mg 

According to another aspect of the present embodiment, the compositionis made into a dosage form for oral administration. The dosage form isselected from capsule, paste, ointment, infusion, injection, ampoule,solution, suspension, emulsion, oil, or, cream. The composition isadministrable to human beings at a dose of 50 mg to about 2000 mg.

In some embodiment an analgesic and anti-inflammatory composition madeof extract of Curcuma longa or curcuminoid composition and sesame oil.The composition is a homogenised dispersion of turmeric extract insesame oil.

An aspect of the embodiment is the proportion of each component in thecomposition; extract of Curcuma longa or curcuminoid composition tosesame oil is blended in 1:1 to 1:99 ratio, more preferably 1:1 to 1:10by weight. Some other preferred ratios are 2:3, 5:7 or 11:19.

Another aspect of the embodiment is that, the extract of Curcuma longaor curcuminoid composition have a specific-surface-area (SSA) of morethan 900 m²/Kg more preferably above 3000 m²/Kg. The SSA of the extractof Curcuma longa or curcuminoid composition dispersed in lipid solutionis 5 to 15 fold greater than regular boswellia extract, more precisely 9to 12 fold. The average particle size of dispersed boswellia extract isless than 20μ-1μ, more precisely than 50% of dispersion has a particlesize less than 5 μl.

Another aspect of the embodiment is the curcuminoid composition; it ismade of a combination of curcuminoids and essential oil of turmeric. Theessential oil of turmeric comprises ar-turmerone at least 15% andα-turmerone at least 15%. The maximum limit for ar-turmerone andα-turmerone can go up to 50%.

According to another aspect of the present embodiment, the compositionis made into a dosage form for oral administration. The dosage form isselected from capsule, sachet, paste, ointment, infusion, injection,ampoule, solution, suspension, emulsion, oil, or, cream. The compositionis administrable to human beings at a dose of 50 mg to about 2000 mg.

In some embodiment a method to make the composition with water-insolubleboswellia extract, extract of Curcuma longa or curcuminoid compositionand sesame oil is disclosed. Said method comprises (refer to FIG. 6);(1) mixing boswellia extract (powder) and curcuminoid composition(powder) in 3:1 ratio, (2) The mixture is blended with sesame oil in 2:3ratio by weight, (3) Pass the 2:3 blend through a bead mill, (4) checkfor particle size of the blend and pass blend through bead mill till theaverage particle size of less than 5-2 μm is obtained. In someembodiment an anti-oxidant can also be added to improve the shelf lifeof the active components.

An aspect of the embodiment is water-insoluble boswellia extract andcurcuminoid composition. Water-insoluble boswellia extract is made ofover 30% boswellic acid, more precisely at least 10% AKBA, less than 1%KBA, 5-12% α-BA and 19-28% β-BA. Curcuminoid composition is made ofcombination of curcuminoids and essential oil of turmeric. The essentialoil of turmeric comprises ar-turmerone at least 15% by weight orα-turmerone at least 15% by weight or both. The composition is ahomogenised dispersion of Water-insoluble boswellia extract andcurcuminoid composition in sesame oil.

In some embodiment a method to make the composition with enhancing painrelief activity of water-insoluble boswellia extract, and sesame oil isdisclosed. Said method comprises (refer to FIG. 5); (1) mixing boswelliaextract (powder) and sesame oil in 2:3 ratio by weight, (2) Pass the 2:3blend through a bead mill, (5) check for particle size of the blend andpass blend through bead mill till the average particle size of less than5-2μ, is obtained. In some embodiment an anti-oxidant can also be addedto improve the shelf life of the composition.

An aspect of the embodiment is water-insoluble boswellia extract.Water-insoluble boswellia extract is made of over 30% boswellic acid,more precisely at least 10% AKBA, less than 1% KBA, 5-12% α-BA and19-28% β-BA. The composition is a homogenised dispersion ofWater-insoluble boswellia extract in sesame oil.

In some embodiment a process to make boswellia extract with 10% AKBAcomprises (Refer to FIGS. 2 and 3) is disclosed. Subject boswelliafrankincense to steam distillation, volatile oil is removed in theprocess. Water soluble part is removed when water used for distillationis filtered out leaving behind solid residue. The solid residue issubjected to Ethyl acetate to obtain a supernatant. NaOH added in thesupernatant, then the supernatant is subjected to liquid-liquidextraction. The boswellic acid is converted to boswellic sales and thesalt is dissolved in water. The water part and Ethyl acetate part isseparated and water part is taken forwards. HCL is added to the waterpart and a precipitate is formed. The precipitate is dried to obtainboswellia extract.

In some embodiment a process to enrich AKBA in boswellia extract withoutacetylation. Powdered of boswellia extract with 10% or less AKBA ismixed with ethyl acetate and blended with silica adsorbent. The ethylacetate dried off and the silica gel is loaded into a preconditionedsilica column. The column is initially eluted with Hexane and Hexanefraction is collected as Elute 1. Then the column is eluted withdifferent ratio of Hexane and Ethyl acetate mixture:Elute 2—Hexane:Ethylacetate 95:5; Elute 3—Hexane:Ethyl acetate 90:10; Elute 4—Hexane:Ethylacetate 80:20; Elute 5—Hexane:Ethyl acetate 70:30; Elute 6—Hexane:Ethylacetate 60:40; and Elute 7—Hexane:Ethyl acetate 20:80. The column isfinally eluted with 100% Ethyl acetate as Elute 8.

An elute for each mixture is collected (from Elute 2 to Elute 7),separated and tested for boswellic acids. The Elute 2 is the mixture of80% beta boswellic acid and 20% alpha boswellic acid, elute 3 is themixture of beta-boswellic acid, alpha boswellic acid and 3-0-acetylboswellic acid, elute 4 is the mixture of, alpha boswellic acid,3-O-acetyl boswellic acid and acetyl ketoboswellic acid (AKBA), elute 5is the mixture of 70% acetyl ketoboswellic acid and 30% ketoboswellicacid, elute 6 is the mixture of 10% acetyl ketoboswellic acid. TheElutes are blended in such a manner to get a ratio of E1, E2 andE3:E1—is just Elute 5, (AKBA70%), E2—is a mix of Elute5 and Elute 4(1:1) (AKBA60%), E3—is a mix of Elute5 and Elute 4(1:5) (AKBA50%).

FIG. 1 shows an extraction process to extract boswellia extract forboswellia gum resin. The boswellia gum resin is loaded into a reactionchamber and to the reaction chamber required amount of n-Hexane is alsoadded. The boswellia resin is washed with the n-hexane in the chamber.The n-hexane part is filtered out and the reaming residue is takenforward. The residue is again loaded in to a reaction chamber and isextracted with methanol. The methanol part is filtered out and collectedand the reaming residue is extracted two more time with fresh methanolin the same manner. All the methanol part are collected and concentratedunder vacuum, the residue is discarded. The concentrate is dried toobtain a powdered menthol extract of boswellia gum resin. The finalproduct is also called the sample 3.

FIG. 2 shows steam distillation process of boswellia gum resin. The rawmaterial of the steam distillation is boswellia gum resin. The rawmaterial is fed in to the distillation unit. Through simple distillationthe volatile is separated out from the top. After distillation the waterin the distillation unit is drained out, water soluble part in the rawmaterial is removed along with the drained water from the distillationunit. The remaining solid residue in the distillation unit is removedand dried. The dried residue is sample 1.

FIG. 3 Sample 1 is used as raw material, sample 1 is charged in to areactor from the top. Ethyl acetate is also charged into the reactor.The Sample 1 is subjected to Ethyl acetate for 6 h at 70° C. After 6 hthe Ethyl acetate part is removed and concentrated. In to theconcentrate NaOH is added, this will result in the formation ofBoswellic salts. The Ethyl acetate part is taken forward for aliquid-liquid extraction with water as other solvent. The Boswellicsalts get extracted by the water and the water part is taken forward.The Ethyl acetate part after the liquid-liquid extraction is recycled tosample 1 reaction chamber. On to the water part adequate amount of HCLto for precipitate. The precipitate is removed and dried. The driedprecipitate is the Ethyl acetate extract, also known as Sample 2.

FIG. 4 Sample 3 is dissolved in Ethyl acetate and mixed with HP 20resin. Once mixed well the Ethyl acetate is dried off. The resin withSample 3 is loaded on to a silica column. The column is first extractedwith 100% Hexane, a elute 1 is obtained. Then with a mixture of hexaneand ethyl acetate 95:5 ratio to obtain elute 2. Then with a mixture ofhexane and ethyl acetate 90:10 ratio to obtain elute 3. Then with amixture of hexane and ethyl acetate 80:20 ratio to obtain elute 4. Thenwith a mixture of hexane and ethyl acetate 80:20 ratio to obtain elute5. Then with a mixture of hexane and ethyl acetate 70:30 ratio to obtainelute 6. Then with a mixture of hexane and ethyl acetate 60:40 ratio toobtain elute 7. Then with a mixture of hexane and ethyl acetate 20:80ratio to obtain elute 8. Then with 100% ethyl acetate to obtain elute 9.

FIG. 5 A boswellia extracts about 40 Kg, sesame oil 60 Kg andantioxidant about 2000 ppm are taken and they are loaded onto a highspeed mixture. The mixture obtained is passed through bead mill toobtain a homogenized mixture. The mixture passed through bead mill onceis called BS-1 and the mixture passed twice is called BS-2 and the beadmill passed thrice is called BS-3 and the mixture passed four times iscalled BS-4.

FIG. 6 shows a boswellia extract and curcumin composition is mixed in3:1 ratio. The curcuminoid composition mentioned as curcumin complex inFIG. 6. The 3:1 mixture is taken forward; about 40 Kg of the mixture ismixed with 60 Kg of sesame oil in a high speed mixture. 2000 ppm ofantioxidant is also added to the mixture. The mixture from the highspeed mixture is taken forward and passed through the bead mill. Ahomogenized mixture of boswellia extract, curcuminoid composition andsesame oil is obtained from the bead mill.

FIG. 7 shows two graphs indicating the change in Numerical Rating Scale(NRS) score with time. Graph (a) indicates the change in NRS score amongpatients within 6 hours of administration of the drug. The drugadministered are BSC-4 and Paracetamol to two different groups ofpatents. At the baseline the NRS score for patients was around 6. TheNRS score went down to 2 for both groups of patents in six hours. Ingraph (b) indicates the change in NRS score among patients within 7 daysof regular use of drug. The base line score in this case was also closeto 6, by the end of 7^(th) day the NRS score in both groups went done toclose to 1.

FIG. 8 shows two graphs indicating the change in Pain Relief Scale (PRS)score with time. Graph (a) indicates the change in PRS score amongpatients within 6 hours of administration of the drug. The drugadministered are BSC-4 and Paracetamol to two different groups ofpatents. At the baseline the PRS score for patients was around 1. ThePRS score went up to 3 for both groups of patents in six hours. In graph(b) indicates the change in PRS score among patients within 7 days ofregular use of drug. The base line score in this case was close to 1, bythe end of 7^(th) day the PRS score in both groups went done to close to3.

FIG. 9 shows two graphs indicating the time for perceptible pain relief(PPR) and meaningful pain relief (MPR). The drug administered are BSC-4and Paracetamol to two different groups of patents. It's a horizontalbar graph first showing the extent of time in each case of PPR and MPRfor both groups.

FIG. 10 shows patients Global Impression of Change Post Dose (GICPD).It's a vertical bar graph showing GICPD of each day till day 7 and foreach group of BSC-4 and Paracetamol patents.

The significance of the sesame seed oil blend with boswellia andcurcuminoid composition is illustrated through animal study. Theincrease in efficacy of plant part when blended with sesame seed oil isillustrated in animal studies provided. Ability to improvebioavailability and activity of sesame seed oil is also illustrated inthe examples.

Sesame seed oil is obtained through Sesame seed expeller; it can be coldpress or hot press or even solvent extraction. Standard oil has aboutone percent sesame lignan and if required the lignan can be enrichedthrough column chromatography. For the illustration standard sesame seedoil is used which has about one percent lignans.

The examples disclosed below do not limit the scope of the disclosure.

EXAMPLES Example 1

The Method to Enrich AKBA to 10% without Alkylation is Described in FIG.2 and FIG. 3

Boswellia frankincense pellets were used for the extraction. About 1000Kg of pellets were subjected to steam distillation. The essential oilwas collected separately and water used for distillation was drained outfrom the apparatus, water-soluble part was removed in this way. Theresidue was dried under vacuum to obtain Sample-1. This was the inputmaterial for the process shown in FIG. 3. For Ethyl acetate extraction,a reactor was charged with sample-1, along with double the quantity ofEthyl acetate. The reactor was heated to about 70° C. for about 6 h ortill the desired TDS was obtained. The reactor supernatant and residuewas formed; the supernatant was filtered out the reactor. Thesupernatant was cooled to room temperature and a fixed amount of NaOHgroup was added. The Supernatant was subjected to liquid-liquidextraction with deionized water as another solvent. The Ethyl acetateand water part was separated out and the water part was taken forward.HCL was added to the water part and precipitate was formed. Theprecipitate was separated out and dried under vacuum. The dried extractwas pulverized to get 350 kg of fine powder called as Sample-2.

The fine powdered powder, Sample-2, was the Boswellia extract with 10%[5%] AKBA, 1-3% β-BA, 0.1-0.4% KBA and total boswellic acid was about35-40% (AKBA10). The final product obtained was immiscible in water. Theaverage SSA of the final powdered extract was less than 120 m²/Kg.

Example 2 The Method of Extracting Boswellia Resin as Shown in FIG. 1Illustrated.

Boswellia gum resin was used for the extraction. About 1000 Kg of gumresin pellets was loaded into a reactor and was subjected to three timesthe quantity of hexane for about 5 hours. The hexane part was separatedfrom the residue and oil gets separated along with hexane. The residuewas subjected to methanol extraction; two times the quantity of methanolwas added into the reactor. The reactor was heated for about 6 h at 70°C., (total dissolved solids) TDS was monitored continuously. Asupernatant and residue was formed; supernatant was filtered out andconcentrated. The residue was extracted two more times with methanol.All superannuates were collected and concentrated. A powdered methanolextract of boswellia was obtained, called as sample 3.

The extract, Sample 3, has about 2-4% AKBA, 17-20% β-BA, 4 to 7% KBA andtotal boswellic acid was about 30-35% (AKBA2). The powdered extract washydrophobic in nature and had an average SSA of less than 100 m²/Kg. Theextract was lipid soluble.

Example 3 Process to Purify AKBA for Boswellia Extract as Described inFIG. 4:

Powder of boswellia extract from example 2(sample 3) was mixed withethyl acetate and blended with silica adsorbent. The ethyl acetate driedoff and the silica gel was loaded into a preconditioned silica column.The column was initially eluted with Hexane and Hexane fraction wascollected as Elute 1. Then the column was eluted with different ratio ofHexane and Ethyl acetate mixture:

Elute 2—Hx:EA 95:5;

Elute 3—Hx:EA 90:10;

Elute 4—Hx:EA 80:20;

Elute 5—Hx:EA 70:30;

Elute 6—Hx:EA 60:40; and

Elute 7—Hx:EA 20:80.

The column was finally eluted with 100% Ethyl acetate as Elute 8. Anelute for each mixture was collected (from Elute 2 to Elute 7),separated and tested for boswellic acids.

The Elute 2 was a mixture of 80% beta boswellic acid and 20% alphaboswellic acid, elute 3 was a mixture of beta-boswellic acid, alphaboswellic acid and 3-O-acetyl boswellic acid, elute 4 was a mixture of,alpha boswellic acid, 3-O-acetyl boswellic acid and acetyl ketoboswellicacid (AKBA), elute 5 was a the mixture of 70% acetyl ketoboswellic acidand 30% ketoboswellic acid, elute 6 was a the mixture of 10% acetylketoboswellic acid.

The Elutes were blended in such a manner to get a ratio of E1, E2 andE3;

E1 Elute 5 alone, (AKBA70);

E2—combination of Elute5 and Elute 4 (1:1) (AKBA60);

E3—combination of Elute5 and Elute 4(1:5). (AKBA50).

Sample 2 or sample 1 could have also been used for this process.

Example 4 Method of Preparing Dispersion of Boswellia in Sesame Oil isDescribed in FIG. 5.

About 5.6 kg Sesame oil was taken; oil had about 1 to 0.9% sesamelignans. To this, 2000 ppm (of 10 kg) of natural anti-oxidant was addedand mixed well. About 4.4 kg Boswellia extract made as per example1(sample 2) was weighed and gradually added in the above Sesame oilunder continuous mixing in the high-speed mixing vessel to obtain ablend. The blend thus made was passed through a bead mill, in the beadmill the strong inter-movements of grinding media form great shearing,pressing and abrasive force, making the material change shape andgenerate stress-field. When that stress reaches material breading limit,the material was pulverized. The blend was passed through the bead millseveral times. At each pass through the bead mill a sample was collectedfor study. The samples selected for studies were; BS-1 (200-500 m²/kg)from first pass; BS-2 (700-1000 m²/kg) from second pass, BS-3 (1100-1300m²/kg) from third pass and BS-4 (>1300 m²/kg) from fourth pass.

The above-said illustration is not limited by the boswellia extract ofexample 1. But boswellia extract of example 2 and example 3 were alsoused to make such homogenized blend.

Table below show the composition of the final product (a dispersion).

TABLE 2 Composition of the dispersion Sesame oil 5.6 Kg sesame lignans50 gm Boswellia 4.4 Kg AKBA 440 gm  KBA 18 gm anti-oxidant 2000 ppm

Example 5 Method of Making Micron Size Composition of Boswellia Acid,Sesame Lignin and Curcuminoid.

About 6 kg Sesame oil was taken as a source of sesame lignans. Thesesame oil had 1 to 0.9% sesame lignans. About 3.0 kg Boswellia extractmade as per example 1 was weighed and gradually added in the aboveSesame lignin under continuous mixing in the high-speed mixing vessel.1.0 kg curcuminoid composition 95% purity extract was weighed andgradually added in the above oil under continuous mixing in thehigh-speed mixing vessel. To this, 2000 ppm (of 10 kg) of naturalanti-oxidant was added and mixed well to obtain a blend. The blend thusmade was passed through a bead mill, in the bead mill the stronginter-movements of grinding media form great shearing, pressing andabrasive force, making the material change shape and generatestress-field. When that stress reaches material breading limit, thematerial was pulverized. The blend was passed through the bead millseveral times. At each pass through the bead mill a sample was collectedfor study.

The samples selected for studies are; BSC-1 (80-100 m²/kg) on firstpass; BSC-2 (200-400 m²/kg) on second pass; BSC-3 (600-800 m²/kg) onthird pass; and BSC-4 (>900 m²/kg) on forth pass.

Composition of the BSC samples provided in table (a dispersion).

TABLE 3 Composition of the dispersion Sesame oil 6 Kg sesame lignans  54gm Boswellia 3 Kg AKBA 300 gm KBA  12 gm Curcuminoid 1 Kg Curcuminoids884 gm Turmeric oil  70 gm anti-oxidant 2000 ppm

Example 6

Boswellia Extract Simple Blend with Vegetable Oils.

The sample 2 from example one was blended with various vegetable oils ina 2:3 ratio. The blends so made were used as test samples for activitystudy.

Sample 2 was separated into six batches of 10 Kg each; a, b, c, d, e andf. Each batch was blended with a different oil about 15 Kg each, theoils were selected from a group of sesame seed oil, olive oil, rice branoil, and coconut oil, cotton seed oil, and boswellia fat. The batch withsample 2 blended with sesame oil was loaded onto a high speed mixtureand mixed well to obtain a blend F1. The same process is repeated toobtain F2, F3, F4, F5 and F6.

List of boswellia blend with various oils.

TABLE 4 F1 sesame seed oil F4 coconut oil F2 olive oil F5 cotton seedoil F3 rice bran oil F6 boswellia fat

Each combination was in a 2:3 ratio of boswellia extract to vegetableoil. As such no uniform mixture was obtained rather a colloid system wasformed. The averages SSA of such samples were below 200 m²/kg.

Example 7

Animal Study Comparing Various Blends of Boswellia Extract, with EdibleOils for their Anti-Inflammatory Activity.

The animals were housed in polypropylene cages and maintained understandard animal house conditions (12:12 hour light/dark cycle at 24±2°C. and 45-65% relative humidity). The rats had free access to standardpellet diet and water. 24 rats were divided into 8 groups comprising of3 rats in each group. The rats were deprived of food, but had freeaccess to drinking water for 12 h prior to the experiment. The treatmentwas as follows:

After 12 hour fasting, baseline paw volume was recorded for each ratusing digital plethysmometer (Ugo Basile, Germany). Carrageenan (0.1 mlof 1%) in saline (0.9% NaCl) was injected into the plantar surface ofthe right hind paw of the animals. The experimental groups were giventhe designated extract/standard orally, 30 minutes prior to theinjection of the carrageenan. After injection of carrageenan, paw volumewas recorded at 3 hr. to 6 hr. post carrageenan. The edema was expressedas an increase in the volume of paw from baseline value, and thepercentage of inhibition for each rat was calculated.

Each composition of boswellia was obtained through standard mixing ofboswellia extract with vegetable oil.

Group 1: 10 mg/Kg Diclofenac.

Group 2: 82 mg/Kg Hydrophobic blend of Boswellia extract (10% AKBA) withsesame oil (2:3).

Group 3: 82 mg/Kg Hydrophobic Boswellia extract (10% AKBA) with coconutoil (2:3).

Group 4: 82 mg/Kg Hydrophobic Boswellia extract (10% AKBA) with oliveoil (2:3).

Group 5: 82 mg/Kg Hydrophobic Boswellia extract (10% AKBA) with ricebran (2:3).

Group 6: 82 mg/Kg Hydrophobic Boswellia extract (10% AKBA) with Cottonseed oil (2:3).

Group 7: 82 mg/Kg Hydrophobic Boswellia extract (10% AKBA) withBoswellia fat (2:3).

Group 8: 50 mg/Kg Homogenized dispersion hydrophobic Boswellia extractwith 10% AKBA with sesame oil with 10% sesame lignans. (BS-4).

Percentage inhibition of Inflammation on administration of a mixture ofBoswellia extract with various oil.

TABLE 5 Percentage Avrage Rat dose inhibition (%) percentageCompositions (mg/kg) 3HR 6HR inhibition Diclofenac 10 66.67 69.94 68.3Boswellia extract (10% 82 60.9  62.59 62 AKBA) + Sesame oil Boswelliaextract (10% 82 57.76 59.27 59 AKBA) + Coconut oil Boswellia extract(10% 82 53.33 49.33 51.33 AKBA) + Olive oil Boswellia extract (10% 8229.29 27.36 28.32 AKBA) + Rice bran oil Boswellia extract (10% 82 44.9547.88 46 AKBA) + Cotton seed oil Boswellia extract (10% 82 37.12 41.2139 AKBA) + Boswellia fat BS-4 50 44.48 93.4  69

The results indicate that among all the oil blended with boswelliaextract, it was the sesame oil blend which had the highest activity.Sesame oil was able to enhance the activity of compositions derived fromplant parts. Study conducted with other plant part blended withboswellia oil gave similar results. Sesame oil was able to enhancebioactivity of water insoluble compounds of plants. The blends were alsocompared with BS-4 which has a much higher efficacy than the otherentire blend at a lower dose of 50 mg.

Example 8

Animal Study Comparing Boswellia Extract, Sesame Oil and their VariousCombinations for their Anti-Inflammatory Activity.

The animals were housed in polypropylene cages and maintained understandard animal house conditions (12:12 hour light/dark cycle at 24±2°C. and 45-65% relative humidity). The rats had free access to standardpellet diet and water. 42 rats were divided into 9 groups comprising of3 rats in each group. The rats were deprived of food, but had freeaccess to drinking water for 12 h prior to the experiment. The treatmentwas as follows:

Group 1: Untreated control.

Group 2: 10 mg/Kg Diclofenac.

Group 3: 20 mg/Kg Hydrophobic Boswellia extract with 2% AKBA (made asper example 2).

Group 4: 20 mg/Kg Hydrophobic Boswellia extract with 10% AKBA (made asper example 1).

Group 5: 30 mg/Kg Sesame seed oil about 0.9% sesame lignans.

Group 6: 50 mg/Kg Simple blend of Boswellia extract with 2% AKBA withSesame seed oil with 10% sesame lignans (made as per example 6; usingAKBA2).

Group 7: 50 mg/Kg Homogenized dispersion of hydrophobic Boswelliaextract with 2% AKBA with sesame oil with 10% sesame lignans. (Made asper example 4).

Group 8: 50 mg/Kg Simple hydrophobic Boswellia extract with 10% AKBAwith sesame oil with 10% sesame lignans. (Made as per example 6, F1).

Group 9: 50 mg/Kg Homogenized dispersion hydrophobic Boswellia extractwith 10% AKBA with sesame oil with 10% sesame lignans. (Made as perexample 4).

After 12 hour fasting, baseline paw volume was recorded for each ratusing digital plethysmometer (Ugo Basile, Germany). Carrageenan (0.1 mlof 1%) in saline (0.9% NaCl) was injected into the plantar surface ofthe right hind paw of the animals. The experimental groups were giventhe designated extract/standard orally, 30 minutes prior to theinjection of the carrageenan. After injection of carrageenan, paw volumewas recorded at 3 hours to 6 hours post carrageenan. The oedema wasexpressed as an increase in the volume of paw from baseline value, andthe percentage of inhibition for each rat was calculated.

Comparing Boswellia extract, sesame oil and their various combinationsfor their anti-inflammatory activity.

TABLE 6 Average percentage inhibition percentage Groups 1 h 3 h 5 h 6 hinhibition 1 Untreated control. NA NA NA NA NA 2 10 mg/Kg Diclofenac.64% 84% 93% 97% 85% 3 20 mg/Kg Hydrophobic  4% 10%  7%  8%  7% Boswelliaextract with 2% AKBA (SSA < 100 m²/Kg). 4 20 mg/Kg Hydrophobic 17% 42%36% 42% 34% Boswellia extract with 10% AKBA. (SSA < 120 m²/Kg). 5 30mg/Kg Sesame seed oil  9% 29% 28% 29% 24% with 10% sesame lignans. 6 50mg/Kg Simple Blend of 12% 37% 38% 39% 31.5%   Boswellia extract with 2%AKBA with Sesame seed oil with 10% sesame lignans. (SSA < 100 m²/Kg). 7BS-4: 50 mg/kg dispersion of 22% 62% 65% 71% 55% boswellia extract with2% AKBA in Sesame seed oil with 10% sesame lignans. (SSA > 900 m²/Kg). 850 mg/Kg Simple Hydrophobic 25% 68% 69% 72% 58.67%   Boswellia extractwith 10% AKBA with sesame oil with 10% lignans. (SSA < 120 m²/Kg). 9BS-4: 50 mg/Kg dispersion of 44% 64% 81% 94% 70.86%   Boswellia extractwith 10% AKBA in sesame oil with 10% Lignans. (SSA > 900 m²/Kg).

It was observed that the simple blend of Boswellia extract with sesameoil did not show any increase in efficacy, but the inhibition ininflammation seen in simple blend of group 6 and 8 were more or lessclose the added effect of group 4 and 5 or group 4 and 5. Group 6 wasthe counterpart of group 7 and group 8 was the counter part of group 9.The only difference in them was the particle size of boswellia extract.The BS-4 blend of group 7 and 9 with the same quantity of boswellia andsesame oil showed an unexpected improvement in its activity as comparedto its counterpart group 6 and 8. Even with the same components at thesame dose the homogenized blend had a greater efficacy.

Example 9 Activity of Boswellia Dispersion in Different SSA Values.

The animals were housed in polypropylene cages and maintained understandard animal house conditions (12:12 hour light/dark cycle at 24±2°C. and 45-65% relative humidity). The rats had free access to standardpellet diet and water. 15 rats were divided into 5 groups comprising of3 rats in each group. The rats were deprived of food, but had freeaccess to drinking water for 12 h prior to the experiment. The treatmentwas as follows:

After 12 hour fasting, baseline paw volume was recorded for each ratusing digital plethysmometer (Ugo Basile, Germany). Carrageenan (0.1 mlof 1%) in saline (0.9% NaCl) was injected into the plantar surface ofthe right hind paw of the animals. The experimental groups were giventhe designated extract/standard orally, 30 minutes prior to theinjection of the carrageenan. After injection of carrageenan, paw volumewas recorded at 3 hr to 6 hr post carrageenan. The edema was expressedas an increase in the volume of paw from baseline value, and thepercentage of inhibition for each rat was calculated.

-   -   Group 1: 50 mg/Kg BS-1 (SSA 200-500 m²/kg).    -   Group 2: 50 mg/Kg, BS-2 (SSA 700-1000 m²/kg)    -   Group 3: 50 mg/Kg BS-3 (SSA 1100-1200 m²/kg)    -   Group 4: 50 mg/Kg BS-4 (SSA>1300 m²/kg)    -   Group 5: 10 mg/Kg Diclofenac.

Percentage inhibition of Inflammation on administration of a BScomposition at different SSA.

TABLE 7 Percentage Avrage Rat dose inhibition (%) percentageCompositions (mg/kg) 3HR 6HR inhibition BS-1 (SSA 200-500 m²/kg ) 50 2442 34 BS-2 (SSA 700-1000 m²/kg) 50 38 68 53 BS-3 (SSA 1100-1200 m²/kg)50 48. 85 66.5 BS-4 (SSA >1300 m²/kg) 50 67 94 80.5 Diclofenac 10 68 9481

It was observed that as the SSA was increasing the activity was alsoincreasing but it's not a linear increase, only after the SSA went over700 m²/kg a significant increase in activity was observed. BS-1activities were similar to that of a simple blend of boswellia extractwith sesame oil. BS-2, BS-3 and BS-4 are significantly active comparedto their standard counterpart, which was just a boswellia blend withsesame oil. The increased surface area enhances the active sites on theboswellia extract which results better molecular linkage between AKBAand sesame lignans. This results in faster absorption and enhancedactivity of boswellia.

Example 10

Different Ratios of Boswellia and Sesame Oil to Test their Activity.

The animals were housed in polypropylene cages and maintained understandard animal house conditions (12:12 hour light/dark cycle at 24±2°C. and 45-65% relative humidity). The rats had free access to standardpellet diet and water. 27 rats were divided into 9 groups comprising of3 rats in each group. The rats were deprived of food, but had freeaccess to drinking water for 12 h prior to the experiment. The treatmentwas as follows:

After 12 hour fasting, baseline paw volume was recorded for each ratusing digital plethysmometer (Ugo Basile, Germany). Carrageenan (0.1 mlof 1%) in saline (0.9% NaCl) was injected into the plantar surface ofthe right hind paw of the animals. The experimental groups were giventhe designated extract/standard orally, 30 minutes prior to theinjection of the carrageenan. After injection of carrageenan, paw volumewas recorded at 3 hr to 6 hr post carrageenan. The edema was expressedas an increase in the volume of paw from baseline value, and thepercentage of inhibition for each rat was calculated.

Different compositions of sesame oil with boswellia was tested to findout the optimum ratio with enhanced activity.

Each composition of boswellia has undergone a regress milling andgrinding resulting in SSA of greater than 1.2×10³ m²/kg.

Group 1: 50 mg/Kg AKBA10+Sesame oil (2:3).

Group 2: 50 mg/Kg, AKBA10+Sesame oil (5:7)

Group 3: 50 mg/Kg AKBA10+Sesame oil (9:11)

Group 4: 50 mg/Kg AKBA10+Sesame oil (1:3)

Group 5: 50 mg/Kg AKBA10+Sesame oil (1:5)

Group 6: 50 mg/Kg AKBA10+Sesame oil (1:9)

Group 7: 50 mg/Kg AKBA10+Sesame oil (1:1)

Group 8: 50 mg/Kg AKBA10+Sesame oil

Group 9: 10 mg/Kg Diclofenac

Percentage inhibition of Inflammation on administration of a Blend ofboswellia with sesame oil in different ratio.

TABLE 8 Percentage inhibition Average Rat dose (%) percentageCompositions (mg/kg) 3HR 6HR inhibition AKBA10+ Sesame 65 93 79 65 oil(2:3) AKBA10+ Sesame 65 93 79 65 oil (5:7) AKBA10+ Sesame 66 92 79 66oil (9:11) AKBA10+ Sesame 64 91 77.5 64 oil (1:3) AKBA10+ Sesame 63 9076.5 63 oil (1:5) AKBA10+ Sesame 61 86 73.5 61 oil (1:9) AKBA10+ Sesame65 93 79 65 oil (1:1) AKBA10+ Sesame oil Diclofenac 10 66 98 82

The results indicate that boswellia extract dispersion in sesame oil inthe range of 1:1 to 1:9 gives similar results. Among the compositionsprovided AKBA10 in sesame oil in the ratio of 2:3, 5:7 and 9:11 are themost effect.

Example 11 Evaluation of Anti-Inflammatory Activity of Test Samples inCarrageenan Induced Paw Edema in Rats:

SD rats (M/F) weighing 180-220 gm. were selected for the study. Theanimals were acclimatized for a period of five days and they were fedwith standard pellet diet and water ad libitum. After five days ofacclimatization, the rats were deprived of food, but had free access todrinking water for 12 hours prior to the experiment. Right hind paw ofeach rat was marked at the tibio-tarsal junction and baseline paw volumewas determined using a digital plethysmometer (UGO BASILE, ITALY). Ratswere divided into different groups keeping 6 rats in each group. Testsample/standard NSAID/vehicle was fed orally at designated dose. After30 minutes of test sample/standard/vehicle, 0.1 ml carrageenan (1%suspension in 0.9% NaCl) was injected to the animals in subplantarregion of the right hind paw. The paw volume was again determined forall the animals at 6 h after carrageenan injection and percentageinhibition was calculated by using following formula:

${{Percentage}\mspace{14mu}{inhibition}} = {\frac{{\left( {{Vt} - {V\; 0}} \right)\mspace{14mu}{control}} - {\left( {{Vt} - {V\; 0}} \right)\mspace{14mu}{treated}}}{\left( {{Vt} - {V\; 0}} \right)\mspace{14mu}{control}} \times 100}$

-   Group 1: Untreated group.-   Group 2: Diclofenac administered at 10 mg/Kg.-   Group 3: Curcuminoid composition: Containing curcuminoids and    turmeric oil in 12:1 ratio.-   Group 4: Boswellia extract with 10% AKBA from example 2.-   Group 5: Sesame oil with 0.9% Sesame lignans.-   Group 6: Boswellia extract and Curcuminoid composition in 3:1 ratio,    with SSA of 100-120 m²/Kg.-   Group 7: Boswellia extract and Curcuminoid composition and Sesame    oil in 3:1:6, with a SSA of 100-120 m²/Kg.-   Group 8: Boswellia extract and Curcuminoid composition and Sesame    oil in 3:1:6, with a SSA of more than >900 m²/kg.

Where, Vt—was paw volume at particular time point, V0—was the paw volumeat 0 hour (baseline).

TABLE 9 Percentage inhibition in Group Dosage 6 Hours. 1 Untreatedcontrol NA NA 2 Diclofenac  10 mg/Kg 86% 3 Curcuminoid composition:Containing  10 mg/Kg  7% curcuminoids 92.7% and turmeric oil 7.3%. 4Boswellia extract: Containing 10% AKBA.  30 mg/Kg 41% 5 Sesame oil With0.9% Sesame lignans.  60 mg/Kg 20% 6 Boswellia extract and Curcuminoid 40 mg/Kg 50% composition in 3:1 ratio. 7 Boswellia extract andCurcuminoid 100 mg/Kg 64% composition and Sesame oil in 3:1:6, with aSSA of 100 m²/Kg. 8 Boswellia extract and Curcuminoid 100 mg/Kg   96.9%composition and Sesame oil in 3:1:6, with a SSA of more than 0.9 ×10³m²/Kg.

The average percentage inhibition in inflammation in carrageenan inducedrats is shown in table 8. Among all the groups, the test sampleadministered to group 8 animals showed the best results. Group 8 showed32.9 percentage point improvement over group 7 results, although thecomposition of sample administered in group 7 and group 8 animals weresame. The difference between the sample administered in group 7 andgroup 8 was the SSA, SSA of sample administered in group 8 was graterthat 0.9×10³ m²/Kg, whereas the SSA of sample administered to group 7animals was about 100 m²/Kg.

Test sample administered in group 8 was made of boswellia extract,curcuminoid compound and sesame oil. The individual activity boswelliaextract, curcuminoid compound and sesame oil towards inflammation wasprovided in group 3, 4 and 5. The sum of the activity of group 3, 4 and5 was close to 68% (7%+41%+20%), whereas the percentage inhibitionobserved in group 8 was 96.9% that was 28.9 percentage points grater.

It can be concluded that the increase in SSA has enhanced the activityof the boswellia extract, curcuminoid compound and sesame oilcombination composition. The activity was significantly greater that thearithmetically predicted value. This unexpected improvement in activitymight be the result of the synergy created by enhancing the SSA partialsin the composition.

Example 12

Method of Preparation of Essential Oil of Turmeric Enriched withα-Turmerone.

Fresh rhizomes of turmeric (500 Kg) were cleaned. The cleaned turmericrhizomes were flaked. The flaked turmeric was distilled using water(2500 L) in a vessel. Water was boiled up to 64° C. under stirringcondition. Flaked turmeric was added in to the boiled water and stirredfor 15 minutes. Then allowed for soaking for 30 minutes. After soaking,the mixture was heated up to 97° C. Distillation started and oil alongwith water was collected in a separator. Floating oils were collectedand contains 30% α-turmerone, 17% Ar-turmerone and 16% β-turmerone.

Example 13

Method of Preparation of Essential Oil of Turmeric with EnrichedAr-Turmerone.

The rhizomes of turmeric (500 Kg) were dried. The dried turmericrhizomes were powdered to form powdered turmeric. The powdered turmericwas treated with ethyl acetate (1500 L) to form a solution. Theextraction was carried out at 78° C. temperature for 1 hr. After initialextraction, the extraction process was repeated 4 more times and theresultant solution was filtered and the solvent was stripped from thefiltered solution to form an extract. This extract was cooled to about4° C. to obtain crystals of curcuminoid mixture (20 Kg) and a liquid.The crystals of curcuminoid were isolated from the liquid by filtration.

The remaining liquid included the essential oil of turmeric and a resin.The liquid was then steam distilled to isolate essential oil of turmericwith 10-15% Ar-turmerone (25 Kg) and alpha turmerone about 4%. Throughfractionation the purity of Ar-turmerone can be raised to over 45%.

Example 14 Method of Preparing Turmeric Extract.

The rhizomes of turmeric (300 Kg) were dried. The dried turmericrhizomes were powdered to form powdered turmeric. The powdered turmericwas treated with ethyl acetate (900 L) to form a solution. Theextraction was carried out at 78° C. temperature for 1 hr. After initialextraction, the extraction process was repeated 4 more times and theresultant solution was filtered and the solvent was stripped from thefiltered solution to form an extract. This extract was cooled to about4° C. to obtain crystals of curcuminoid (12 Kg) and a liquid. Thecrystals of curcuminoid were isolated from the liquid by filtration. Thecrystals included a mixture of curcumin, demethoxycurcumin andbisdemethoxycurcumin. 95% of the crystals were composed of the mixtureof curcumin, demethoxycurcumin and bisdemthoxycurcumin. The crystalswere powdered to form powdered curcuminoid mixture. The powderedcurcuminoid mixture was also referred to as regular turmeric extract.

Example 15 Method to Prepare Curcuminoid Composition.

The curcuminoid powder prepared as per Example 14(4.2 Kg) was suspendedin water (15 L) to form a suspension. Fraction of essential oilcontaining Ar-turmerone prepared as per Example 13(0.35 Kg) was added tothe suspension in 12:1 ratio. The mixture was pulverized in a colloidalmill to form fine slurry. Water was stripped from the slurry under heatand vacuum to form a uniform blend (4.55 Kg) having curcuminoid mixtureand essential oil containing Ar-turmerone.

Example 16

A Randomized Active Controlled Study to Assess the Efficacy of SesameOil Loaded with Boswellia Extract and Curcuminoid Composition (BSC-4) inAdult Patients with Acute Musculoskeletal Pain.

Sample size for the study: 88 Subjects were randomized with 1:1 ratio ofmale and female in each group. Subject selection—Subjects were selectedfrom the screening site who were ready to give a voluntary informedconsent and who meets study inclusion criteria.

Inclusion Criteria

-   1. Adult patient, Male or female between 18-65 years of age.-   2. A score of 5 or above on the Numerical Rating Scale.-   3. Patients having acute musculoskeletal pain which occurred within    24 hours before presentation e.g. headache musculoskeletal injuries,    myalgia, neck pain, limb pain, low back pain, joint pain, widespread    musculoskeletal pain, painful uncomplicated acute soft tissue injury    of the upper or lower extremity, including acute injuries of    ligaments, tendons, or muscles (including Grade 1), not requiring    admittance to hospital.-   4. Willing to give voluntary informed consent.

Informed consent—The subjects were given the information sheet andexplained in detail about all the aspects of the study. They were givenenough time to consider about joining the study and all their questionswere answered to their satisfaction. There were no coercion of any sortand only those who sign the consent form voluntarily were taken into thestudy.

Visit 1, randomization; subject were provided BSC-4 or Paracetamol asper the pre-documented randomization list accessed only by pharmacist.Patients were entering the NRS, PRS, and PGIC in the diary before andafter 2 hour of taking the dose. Follow up calls were made over phonefor patents compliance to treatment, diary completion. The follow up onday 3 the patient were reminded to bring the diary for review and bottlefor IP accountability at the next visit.

Visit 2, Physical examination, vitals, and patient diary were checked.Post dose (2 hours) pain intensity using NRS, pain relief usingcategorical PRS, and patient's global impression of change (PGIC) wererecoded.

Visit 3, next visit on 6^(th) day from the visit 1, Patients entered theNRS, PRS, and PGIC in the diary before and after 2 hrs of taking thedose. Follow up calls were made over phone for their compliance totreatment, diary completion. The follow up on day 6 the patient werereminded to bring the diary for review and bottle for IP accountabilityat the next visit.

Physical examination, vitals, and patient diary were checked. Post dose(2 hours) pain intensity using NRS, pain relief using categorical PRS,and patient's global impression of change (PGIC) were recorded.

Assessment

Numerical Rating Scale for Pain (NRS)

The NRS is an 11-point scales in which 0 represents ‘no pain’ and 10represents the worst pain possible. The patient were asked to rate theirpain intensity as a number from 0 to 10. Alternatively, for betterconception it may be explained as below.

TABLE 10 Scale Severity 10  Worst Pain 9 Severe 8 7 6 Moderate 5 4 3Mild 2 1 0 No pain

The NRS were recorded on screening and those patients who have 5 orabove score only were enrolled into the study. After the first dose thepatient were give the pain intensity rating every 30 minutes up to 6hours post dose for calculating SPID 6 hrs. The NRS for each hour inprovided in FIG. 7 (a). The percentage change in pain is provided intable below.

TABLE 11 Percentage change in pain intensity at 6 hours BSC-4Paracetamol 71.3 72.1

The NRS was included in the diary and the patient was required to givethe pain intensity every morning before taking the dose and 2 hrs afterdose until the end of the study. The average of the recorded data isprovided in a graphical form in FIG. 7 (b). The average percentagechange of patents when they visited the centre on day 3 and day 7 isprovided below.

TABLE 12 Percentage change in pain intensity in 7 days BSC-4 Paracetamolday 3 23.15 24.8  day 7 81.28 83.62

Pain Relief Scale (PRS)

The pain relief scale is a categorical scale having a positiveprogression from ‘No relief’ to ‘complete relief’.

TABLE 13 Code Category 1. No Relief 2. A Little Relief 3. Some Relief 4.A Lot of Relief 5. Complete Relief

After the first dose the patient rated the pain relief every 30 minutesup to 6 hours for the assessment of Total pain relief 6 hours. Theaverage pain relief score for the 6 hours test was recorded andrepresented in graphical form in FIG. 8 (a). The average percentagechange in pain relief score after 6 hours was recorded and provided inthe table below.

TABLE 14 Percentage change in pain relief at 6 hours BSC-4 (n = 44)Paracetamol (n = 44) >75% (n = 28) >75% (n = 30)

The pain relief scale was included in the diary and the patient wasrequired to give the pain relief every morning before taking the doseand 2 hours after dose until the end of the study. The average painrelief score for the seven days test was recorded in diary andrepresented in graphical form in FIG. 8 (b). The average percentagechange in pain relief score after 3 days and 7th day was recorded andprovided in the table below.

TABLE 15 Percentage change in pain relief BSC-4 (n = 44) Paracetamol (n= 44) Day 3 >50% (n = 21) >50% (n = 20) Day 7 >75% (n = 40) >75% (n =37)

After dosing the two stop watches were given to the patient. The patienthad to stop one of the watches when he felt relief from pain. This timewas taken as the Time to Perceptible Pain Relief (PPR). The averageperceptible pain relief in hour is provided in the table below.

TABLE 16 Perceptible pain relief in hour BSC-4 Paracetamol 2.53 2.62

The second watch was stopped when the patient felt that an adequate painrelief has been achieved. This time was taken as the Time to MeaningfulPain Relief (MPR). If however, MPR was not reached within 6 hours, itwas censored at that time point. The average meaningful pain relief inhours is provided in table below and also depicted in graphical form inFIG. 9.

TABLE 17 Meaningful pain relief in hour BSC-4 Paracetamol 4.46 4.51

Patients Global Impression of Change (PGIC)

In this scale, the patient was asked to rate his overall status sincethe beginning of treatment.

TABLE 18 Count Category 1. Very Much Improved 2. Much Improved 3.Minimally Improved 4. No Change 5. Minimally Worse 6. Much Worse 7. VeryMuch Worse

PGIC was included in the patient diary and the patient had given theimpression of change every morning before taking the dose and 2 hrsafter the dose until the end of the study. The PGIC score was recordedin diary every day for seven days and is provided in table below and thedata is also showed in FIG. 10.

TABLE 19 Day 2 3 4 5 6 7 BSC-4 3 3 3 3 3 2 Paracetamol 3 3 3 3 3 2

Significant improvement in pain was observed in all the parameterstested for both the group of BSC-4 and Paracetamol. The efficacy ofBSC-4 was observed to be at par with that of Paracetamol. Not only BSC-4showed clinically significant results but also demonstrates that it canact as an alternative to Paracetamol for pain.

1.-37. (canceled)
 38. An analgesic and anti-inflammatory composition,prepared by a method comprising: a. mixing (i) a solid extract ofBoswellia and (ii) a solid comprising one or more of an extract ofCurcuma longa, a curcuminoid composition and combinations thereof toobtain a blend; b. adding the blend to a sesame seed oil to obtain afirst mixture; and, c. milling the first mixture to obtain a particlesize of the solids ranging from less than about 20 micrometers to about1 micrometer.
 39. The analgesic and anti-inflammatory composition ofclaim 38, wherein the extract of Boswellia is prepared by a methodcomprising: a) steam distilling gum resin pellets of Boswellia mixedwith water, b) collecting the essential oil from steam distillation, c)draining out water to obtain a first gummy residue, d) extracting thegummy residue with ethyl acetate at about 70° C. to obtain a secondresidue and a first supernatant, e) adding sodium hydroxide in firstsupernatant, f) performing a liquid-liquid extraction of the firstsupernatant with water to obtain a water-soluble phase and an ethylacetate phase, g) adding hydrochloric acid to the water-soluble phase toobtain a precipitate and a second supernatant, h) drying and pulverizingthe precipitate to obtain a powder extract of Boswellia.
 40. Theanalgesic and anti-inflammatory composition of claim 39, wherein theextract of Boswellia comprises about 10% acetyl-11-keto-beta-boswellicacid.
 41. The analgesic and anti-inflammatory composition of claim 40,wherein the extract of Boswellia comprises about 0.1-0.4%11-keto-beta-boswellic acid.
 42. The analgesic and anti-inflammatorycomposition of claim 39, wherein the extract of Boswellia is prepared bya method further comprising: i) dissolving the powder extract ofBoswellia in ethyl acetate to obtain a solution, j) loading the solutiononto a silica column, k) extracting the silica column of step j) withhexane to obtain a first elute and a first eluted column; l) extractingthe first eluted column of step k) with a solvent comprising hexane andethyl acetate in a ratio of about 95:5 to obtain a second elute and asecond eluted column, wherein the second elute comprises about 80% betaboswellic acid and about 20% alpha boswellic acid; m) extracting thesecond eluted column of step l) with a solvent comprising hexane andethyl acetate in a ratio of about 90:10 to obtain a third elute and athird eluted column, wherein the third elute comprises beta-boswellicacid, alpha boswellic acid and 3-O-acetyl boswellic acid; n) extractingthe third eluted column of step m) with a solvent comprising hexane andethyl acetate in a ratio of about 80:20 to obtain a fourth elute and afourth eluted column, wherein the fourth elute comprises alpha boswellicacid, 3-O-acetyl boswellic acid and acetyl-11-keto-beta-boswellic acid;o) extracting the fourth eluted column of step n) with a solventcomprising hexane and ethyl acetate in a ratio of about 70:30 to obtaina fifth elute and a fifth eluted column, wherein the fifth elutecomprises about 70% acetyl-11-keto-beta-boswellic acid and about 30%11-keto-beta-boswellic acid; p) extracting the fifth eluted column ofstep o) with a solvent comprising hexane and ethyl acetate in a ratio ofabout 60:40 to obtain a sixth elute and a sixth eluted column, whereinthe sixth elute comprises about 10% acetyl-11-keto-beta-boswellic acid;q) extracting the sixth eluted column of step p) with a solventcomprising hexane and ethyl acetate in a ratio of about 20:80 to obtaina seventh elute and a seventh eluted column; and r) extracting theseventh eluted column of step q) with ethyl acetate to obtain an eighthelute, wherein the extract of Boswellia is selected from the groupconsisting of the first elute, the second elute, the third elute, thefourth elute, the fifth elute, the sixth elute, the seventh elute, theeighth elute, and combinations thereof.
 43. The analgesic andanti-inflammatory composition of claim 42, wherein the extract ofBoswellia is selected from the group consisting of the fourth elute, thefifth elute, the sixth elute, and combinations thereof.
 44. Theanalgesic and anti-inflammatory composition of claim 42, wherein theextract of Boswellia comprises about 70% acetyl-11-keto-beta-boswellicacid.
 45. The analgesic and anti-inflammatory composition of claim 38,wherein the step of milling of the first mixture provides a uniformblend.
 46. The analgesic and anti-inflammatory composition of claim 45,wherein a total combined specific surface area provided by particles inthe uniform blend ranges from about 900 meter² per kilogram to about3000 meter² per kilogram of the uniform blend composition.
 47. Theanalgesic and anti-inflammatory composition of claim 46, wherein thecomposition is a dosage form, and wherein the dosage form comprisesabout 50% of the uniform blend having a particle size of less than about5 micrometers.
 48. The analgesic and anti-inflammatory composition ofclaim 38, wherein the solid extracts are added to sesame oil in a 1:1 to1:99 ratio by weight.
 49. The analgesic and anti-inflammatorycomposition of claim 38, wherein the sesame seed oil comprises about 30%to about 70% sesame lignans.
 50. The analgesic and anti-inflammatorycomposition of claim 49, wherein the sesame lignans comprises a weightratio of sesamin:sesamolin of about 1:1.
 51. The analgesic andanti-inflammatory composition of claim 38, wherein the curcuminoidcomposition comprises curcumin, demethoxycurcumin, andbisdemethoxycurcumin
 52. The analgesic and anti-inflammatory compositionof claim 51, wherein the curcuminoid composition further comprises anessential oil of turmeric.
 53. The analgesic and anti-inflammatorycomposition of claim 52, wherein the essential oil of turmeric comprisesat least about 15% alpha-turmerone.
 54. The analgesic andanti-inflammatory composition of claim 38, wherein the analgesic andanti-inflammatory composition is a dispersion.
 55. A dosage formcomprising the analgesic and anti-inflammatory composition of claim 38,the dosage form selected from the group consisting of dispersion, hardgel capsule, soft gel capsule, paste, ointment, infusion, injection,ampoule, solution, suspension, emulsion, oil and cream.
 56. An analgesicand anti-inflammatory composition comprising: at least one of (1) anextract of Boswellia or (2) an extract of Curcuma longa, a curcuminoidcomposition and combinations thereof, and, a sesame oil, wherein theanalgesic and anti-inflammatory composition comprises a particle, andwherein a particle size of the particle ranges from less than about 20micrometers to about 1 micrometer.
 57. A method of preparing an extractof Boswellia, the method comprising: a) steam distilling gum resinpellets of Boswellia mixed with water, b) collecting the essential oilfrom steam distillation, c) draining out water to obtain a first gummyresidue, d) extracting the gummy residue with ethyl acetate at about 70°C. to obtain a second residue and a first supernatant, e) adding sodiumhydroxide in first supernatant, f) performing a liquid-liquid extractionof the first supernatant with water to obtain a water-soluble phase andan ethyl acetate phase, g) adding hydrochloric acid to the water-solublephase to obtain a precipitate and a second supernatant, h) drying andpulverizing the precipitate to obtain an extract of Boswellia.